patients using either x-irradiated melanoma cells or a vaccinia 
viral oncolysate of the tumor cells and have demonstrated 
improved survival in patients receiving adjuvant active 
treatment. 
Duke University has demonstrated that specific CTL can be 
generated in vitro by exposing patient lymphocytes to 
autologous tumor cells in the presence of a low dose 
Interleukin-2 (unpublished data). The specific CTL have effected 
cell mediated killing both in vitro and in vivo (unpublished 
data). The killing is major histocompatibility complex (MHC) 
restricted and can be generated from either peripheral blood 
lymphocytes or lymph node cells. Class I MHC proteins are 
involved in the presentation of intracellular antigens to the 
immune system. Thus, suboptimal levels of MHC membrane 
proteins may prevent effective presentation of tumor associated 
antigens. 
2.3 Active Immune Therapy With Gene Modified Tumor 
Recently, methods for improving anti-tumor immune 
responses in cancer patients by gene transduction of tumor cells 
have been proposed. A variety of lymphokine genes have been 
introduced into tumor cells using retroviral vectors as well as 
non-viral delivery methods (12-18). The transduced cells express 
the inserted gene and secrete the specific lymphokine. We have 
recently shown that human breast cancer cells transduced with 
the gene for human IL-2 serve as potent stimulators of specific 
CTL (unpublished data). Gene-altered autologous breast cancer 
cells might well provoke substantial post-immunological 
responses against host tumor burden. 
The purpose of this study is to demonstrate the safety, feasibility, 
and potential efficacy of treating adults with refractory metastatic 
breast cancer by returning to patients their own cancer cells 
which have been transfected with the gene for the expression of 
Interleukin-2 (IL-2). The intent is to stimulate the patient's own 
cytotoxic lymphocytes (CTLs) to react to the reimplanted tumor 
cells in order to develop a specific immune response. The hope 
is that these "trained" and stimulated lymphocytes will circulate 
to destroy not only the reimplanted tumor cells but also residual 
tumor cells in the patient that have not been transfected. 
Lymphocytes from these patients will be harvested after 
treatment with the transfected tumor cells to determine the 
quantity and characteristics of the CTLs that have been generated 
and to clone and expand these lymphocytes in vitro for potential 
use in subsequent therapeutic protocols. 
Recombinant DNA Research, Volume 20 
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